Women who experience symptoms such as fatigue and joint pain may wonder if they have lupus, an autoimmune disease that’s diagnosed nine times more frequently in women than men. Yet lupus can be difficult to diagnose, because many of its symptoms overlap with several other conditions.

“It’s a great imitator. It can look like different diseases or be mistaken for other things,” said Mariko Ishimori, MD, a rheumatologist at Cedars-Sinai. “Part of the confusion is that every patient has a different combination of symptoms.”

About 70% of people with lupus have systemic lupus, which is when the immune system mistakenly attacks healthy tissue. About half of the people with systemic lupus experience organ-threatening disease, in which the heart, lungs, kidneys or brain are targeted by the immune system. In about 10% of people with lupus, the condition only affects the skin. Another 10% of people with lupus develop the condition because of medication, and switching to another drug should resolve their symptoms.

The exact cause of lupus is unknown, but genetic and environmental factors may be involved. It’s most commonly diagnosed in women between the ages of 15 and 45.

“They may have chronic fatigue at a time when they want to have children and run around after kids,” said Caroline Jefferies, PhD, scientific director of the Center for Research in Women’s Health and Sex Differences at Cedars-Sinai. “It can feel like the flu, making it hard to get out of bed.”

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Many people who have lupus don’t realize they have it. Some lupus symptoms are distinct, such as a butterfly-shaped rash on the face. But many symptoms are vague, including joint pain and sensitivity to sunlight.

“Early symptoms are fatigue, aching, rash, swollen glands, shortness of breath and cognitive impairment,” said Daniel Wallace, MD, a rheumatologist at Cedars-Sinai. “For non-organ-threatening lupus, it usually takes several years before the diagnosis is made.”

Researchers at Cedars-Sinai are trying to determine whether an earlier lupus diagnosis could change the trajectory of disease.

“The SMILE study is trying to identify people who might be at risk for lupus in an effort to change the evolution to disease,” Ishimori said. “Would they have more or fewer symptoms if they were on an antimalarial drug? Does earlier treatment make a difference for certain manifestations? We don’t know the answers yet.”

There isn’t one test to confirm whether someone has lupus. Doctors typically use blood tests, urinalysis, physical exams, a patient’s medical history, and sometimes imaging tests and/or a biopsy for diagnosis.

“We bring a lot of different elements together, including symptoms, certain signs on exam and lab results,” Ishimori said. “The interpretation of tests requires some subtlety. It’s not as simple as ‘This test is high, therefore it’s lupus.’”

Doctors may order an antinuclear antibody (ANA) test. A large number of ANAs may be a sign that someone has an autoimmune disease, including—but not limited to—lupus.

“ANA is the best lab test for lupus,” Wallace said. “It’s seen in 98% of lupus cases, but 13% of all people in the United States have an ANA.”

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Antimalarial drugs are the mainstay of treatment, and they help to reduce symptom flare-ups. Other medications may be prescribed, depending on the severity of disease.

“For non-organ-threatening lupus, we use nonsteroidal anti-inflammatory drugs, antimalarials, plus low-dose corticosteroids and immunosuppressants for those with active disease, and occasionally biologics,” Wallace said. “For serious organ-threatening disease, we use high doses of corticosteroids, tapering to the lowest dose for those with active disease. Historically, we’ve used immunosuppressants, but more recently, we’ve been using biologics instead.”

Some immunosuppressants can’t be used during pregnancy.

“We don’t recommend getting pregnant while your lupus is active,” Ishimori said. “For the best outcomes, we recommend getting everything under control before getting pregnant.”

Cedars-Sinai researchers are investigating different aspects of lupus to better understand the disease and find new treatments. Different studies are focused on hormone imbalances in lupus patients, the effects of a family history of lupus on siblings, the effectiveness of drugs such as N-acetylcysteine and the reasons why some patients don’t respond to certain treatments. Studying less-common types of lupus may also provide researchers with insights.

“We’re working on forms of lupus that are due to single-gene defects,” Jefferies said. “One example is COPA syndrome, where a mutation in a single gene can drive lupus-like autoimmune disease, characterized by lung involvement. We can use this form of lupus to better understand lung involvement in lupus.”

People with lupus are at increased risk of coronary artery disease at an earlier age. Researchers are trying to understand why this happens.

“There’s a microvascular component in lupus. How could we treat that better?” Ishimori said. “Are there other associated immune features that might help us recognize it sooner? The goal is early recognition, potential prevention and active treatment.”